(CB2R) Agonists Modulate Neuropathic Pain and Cytokine Expression Jenny Wilkerson

Total Page:16

File Type:pdf, Size:1020Kb

(CB2R) Agonists Modulate Neuropathic Pain and Cytokine Expression Jenny Wilkerson University of New Mexico UNM Digital Repository Biomedical Sciences ETDs Electronic Theses and Dissertations 12-1-2012 Cannabinoid 2 receptor (CB2R) agonists modulate neuropathic pain and cytokine expression Jenny Wilkerson Follow this and additional works at: https://digitalrepository.unm.edu/biom_etds Recommended Citation Wilkerson, Jenny. "Cannabinoid 2 receptor (CB2R) agonists modulate neuropathic pain and cytokine expression." (2012). https://digitalrepository.unm.edu/biom_etds/68 This Dissertation is brought to you for free and open access by the Electronic Theses and Dissertations at UNM Digital Repository. It has been accepted for inclusion in Biomedical Sciences ETDs by an authorized administrator of UNM Digital Repository. For more information, please contact [email protected]. Jenny L. Wilkerson Candidate Biomedical Sciences- Department of Neurosciences Department This dissertation is approved, and it is acceptable in quality and form for publication: Approved by the Dissertation Committee: Erin D. Milligan, PhD, Chairperson James Wallace, PhD Lee Anna Cunningham, PhD Oscar Bizzozero, PhD i CANNABINOID 2 RECEPTOR (CB2R) AGONISTS MODULATE NEUROPATHIC PAIN AND CYTOKINE EXPRESSION by JENNY L. WILKERSON B.S. Biology, Northwest Missouri State University, 2004 DISSERTATION Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Biomedical Sciences The University of New Mexico Albuquerque, New Mexico November, 2012 ii Acknowledgements There are so many people that have helped me throughout my life, making my journey towards obtaining my doctorate possible. First, I need to recognize all those teachers that inspired and encouraged me throughout my schooling. In particular, my first grade teacher, Mrs. Trutzel, stands out, as she spent countless hours privately tutoring me in lesson areas where I needed help. Her tireless dedication to her students is both commendable and honorable in so many ways, and her contribution in my life is truly immeasurable. Secondly, I must acknowledge the team of physicians that mended a physically broken newborn so many years ago, and allowed me the chance of a normal life. It is those physicians, and the medical researchers that developed the life-saving surgical and critical care skills that allowed me to live, that has inspired me to dedicate my professional career towards medical research. My family has been so supportive in me reaching for my dreams throughout the years, even though I know it was bittersweet for them to watch me fly away. Thank you so much for always believing in me, and encouraging me to follow my dreams. My mother is truly amazing, as she allowed me the freedom to become my own person, and to find my own passions in life. I also owe my love of reading and books to my mom, as she ritually took me to our local library to participate in their summer reading program. Both my parents sacrificed so much, so that I may have a good life, and of which, I will never forget. In this time of remembrance, I must honor my late grandmother, Myra Lynn. I was blessed to have her a part of the first 15 years of my life. She was truly an inspiring, iii remarkable, thoughtful and kind person with incredible inner strength, and she is my most important role model. I count myself as blessed to have such phenomenal experiences from being in Girl Scouts, and special thanks goes out to my extended Girl Scout family- you are all amazing women. I am so thankful to both my family and my friends for the love, support, well-wishes, shoulders that were leaned on, and ears that were talked nearly off, throughout this process. My wonderful husband, Jesse, has been my rock and source of strength. Through the years we have been together, he has stood by me, comforted me, and put me and my goals first. He has been willing to follow me wherever I go in life, and does so many little things to help, to make me laugh, and to show his undying love, devotion and support. I cannot express in words how thankful I am to him, and I am excited to see where life takes us from here. The mentoring that I have received at the University of New Mexico has been terrific. I cannot say thank you enough to Dr. Maggie Warner-Washburne, and the UNM Initiatives to Maximize Student Diversity (IMSD) program for the financial support of my first two years of graduate work, and for the mentoring that did not cease after the program. Dr. Linda Saland and Dr. Jim Wallace are both incredible scientists and amazing people in the department of Neuroscience at UNM. They have provided so much guidance in my development as a scientist, and their dedication to teaching the next generation of physicians and basic scientists is evident in the interactions that I have had with each of them. My committee on studies has provided both wonderful praises, as well as a critical eye in my progress, and I greatly thank the members of my committee for iv both. Above all, I owe my P.I. and primary mentor, Erin Milligan, for molding and making me into the scientist that I have become. She has been a wonderful role model through the years. She has believed in me, guided me, and both mentally and financially supported me throughout my years in her laboratory. She pushed me to perform beyond my own initial expectations of myself, towards my true potential. Also, she has taught me to personally accept only the highest standards of excellence in my professional development. I am so grateful to have had her has my mentor. I also am very much indebted to all the past and present laboratory personnel that I have had the pleasure to work with and come to know. Each one of you, in your own way, left an indelible mark on me, and I thank you for helping me grow as a person, as a scientist, and where appropriate, as a mentor. I must acknowledge the aid that I received from Dr. Clark Bird from UNM department of Neuroscience in his assistance in designing my CB1R primers. I also must thank the marvelous support staff at UNM for so many ‘behind the scenes’ contributions. Thank you to the BSGP staff and the Neurosciences department staff for the administrative support that you have shown me through the years. Thank you to Buz Tyler, who has provided so much invaluable I.T. support, and the Cancer Resource Facility microscopy suite personnel for their expertise on microscopy. Also, a big thank you goes out to the Animal Resource Facility and its staff in doing what you all do, because without it I would not have been able to complete my dissertation. v Table of Contents Dissertation Title Page ....................................................................................... ii Acknowledgements ........................................................................................... iii Abstract ............................................................................................................... x List of Figures .................................................................................................. xiii Abbreviations ...................................................................................................... 1 1. The central role of glia in pathological pain and the potential of targeting the cannabinoid 2 receptor for pain relief .................................................... 4 Abstract ............................................................................................................... 4 1.1 Normal vs. pathological pain ................................................................................................. 6 1.1.1 Acute Pain Signaling ...................................................................................................... 6 1.1.2 Central Sensitization ...................................................................................................... 7 1.1.3 Sensory Changes in Pathological Pain .......................................................................... 9 1.2 The role of glia in pathological pain ....................................................................................... 9 1.2.1 Glial activation ................................................................................................................ 9 1.2.2 Glial morphology and activation markers ..................................................................... 12 1.2.3 Downstream glial signaling of cytokines ...................................................................... 14 1.2.4 Glia in DRG .................................................................................................................. 17 1.2.5 Modulating glial activation for pain relief ...................................................................... 18 1.3 The endocannabinoid system .............................................................................................. 19 1.3.1 Components of the endocannabinoid system .............................................................. 19 1.3.2 Classical cannabinoid receptor signaling ..................................................................... 20 1.3.3 Cannabinoid 2 receptors .............................................................................................. 22 1.3.4 Bioavailability of endocannabinoids ............................................................................. 24 1.3.5 The implications of the endocannabinoid system in pain modulation .......................... 25 1.4 Well-characterized CB2R synthetic compounds .................................................................. 28 1.5 Newer CB2R
Recommended publications
  • 615 Neuroscience-Cayman-Bertin
    Thomas G. Brock, Ph.D. Introduction to Neuroscience In our first Biology classes, we learned that lipids form the membranes around cells. For many students, interests quickly moved to the intracellular constituents ‘that really matter’, or to how cells or systems work in health and disease. If there was further thought about lipids, it might have been limited to more personal issues, like an expanding waistline. It was easy to forget about lipids in the complexities of, say, Alzheimer’s Disease, where tau protein is hyperphosphorylated by a host of kinases before forming neurofibrillary tangles and amyloid precursor protein is processed by assorted secretases, ultimately aggregating to form neurodegenerating plaques. What possible role could lipids have in all this? After all, lipids just form the membranes around cells. Fortunately, neuroscientists study complex systems. Whether working at the molecular, cellular, or organismal level, the research focus always returns to the intricately interconnected bigger picture. Perhaps surprisingly, lipids keep emerging as part of the bigger picture. At least, the smaller lipids do. Many of the smaller lipids, including the cannabinoids and eicosanoids, act as paracrine hormones, modulating cell functions in a receptor-mediated fashion. In this sense, they are rather like the peptide hormones in their diversity and actions. In the neurosystem, this means that these signaling lipids determine if synapses fire or not, when cells differentiate or die, and whether tissues remain healthy or become inflamed. Returning to the question posed above about lipids in Alzheimer’s, these mediators have roles at many levels in the course of the disease, as presented in an article on page 42 of this catalog.
    [Show full text]
  • Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer
    cancers Review Cannabinoids and Endocannabinoid System Changes in Intestinal Inflammation and Colorectal Cancer Viktoriia Cherkasova, Olga Kovalchuk * and Igor Kovalchuk * Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 7X8, Canada; [email protected] * Correspondence: [email protected] (O.K.); [email protected] (I.K.) Simple Summary: In recent years, multiple preclinical studies have shown that changes in endo- cannabinoid system signaling may have various effects on intestinal inflammation and colorectal cancer. However, not all tumors can respond to cannabinoid therapy in the same manner. Given that colorectal cancer is a heterogeneous disease with different genomic landscapes, experiments with cannabinoids should involve different molecular subtypes, emerging mutations, and various stages of the disease. We hope that this review can help researchers form a comprehensive understanding of cannabinoid interactions in colorectal cancer and intestinal bowel diseases. We believe that selecting a particular experimental model based on the disease’s genetic landscape is a crucial step in the drug discovery, which eventually may tremendously benefit patient’s treatment outcomes and bring us one step closer to individualized medicine. Abstract: Despite the multiple preventive measures and treatment options, colorectal cancer holds a significant place in the world’s disease and mortality rates. The development of novel therapy is in Citation: Cherkasova, V.; Kovalchuk, critical need, and based on recent experimental data, cannabinoids could become excellent candidates. O.; Kovalchuk, I. Cannabinoids and This review covered known experimental studies regarding the effects of cannabinoids on intestinal Endocannabinoid System Changes in inflammation and colorectal cancer. In our opinion, because colorectal cancer is a heterogeneous Intestinal Inflammation and disease with different genomic landscapes, the choice of cannabinoids for tumor prevention and Colorectal Cancer.
    [Show full text]
  • Effects of Cannabinor, a Novel Selective Cannabinoid 2 Receptor Agonist, on Bladder Function in Normal Rats
    EURURO-3374; No. of Pages 8 EUROPEAN UROLOGY XXX (2010) XXX–XXX available at www.sciencedirect.com journal homepage: www.europeanurology.com Voiding Dysfunction Effects of Cannabinor, a Novel Selective Cannabinoid 2 Receptor Agonist, on Bladder Function in Normal Rats Christian Gratzke a,b,f, Tomi Streng c, Christian G. Stief b, Thomas R. Downs d, Iris Alroy e, Jan S. Rosenbaum d, Karl-Erik Andersson f,*, Petter Hedlund a,g a Department of Clinical and Experimental Pharmacology, Lund University, Lund, Sweden b Department of Urology, Ludwig-Maximilians-University, Munich, Germany c Department of Pharmacology, Turku University, Finland d Women’s Health, Procter & Gamble Health Care, Cincinnati, OH, USA e Pharmos Limited, Rehovot, Israel f Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA g Urological Research Institute, San Raffaele University Hospital, Milan, Italy Article info Abstract Article history: Background: Cannabinoid (CB) receptors may be involved in the control of bladder Accepted February 19, 2010 function; the role of CB receptor subtypes in micturition has not been established. Published online ahead of Objectives: Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor print on March 1, 2010 agonist, on rat bladder function. Design, setting, and participants: Sprague Dawley rats were used. Distribution of Keywords: CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Cannabinoid Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects Urothelium of cannabinor on rat detrusor and micturition were investigated. Sensory Measurements: Immunohistochemistry, radioligand binding, tritium outflow Detrusor assays, organ bath studies of isolated bladder tissue, and cystometry in awake Cystometry rats were used.
    [Show full text]
  • 2-Arachidonoylglycerol a Signaling Lipid with Manifold Actions in the Brain
    Progress in Lipid Research 71 (2018) 1–17 Contents lists available at ScienceDirect Progress in Lipid Research journal homepage: www.elsevier.com/locate/plipres Review 2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain T ⁎ Marc P. Baggelaara,1, Mauro Maccarroneb,c,2, Mario van der Stelta, ,2 a Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands. b Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy c European Centre for Brain Research/IRCCS Santa Lucia Foundation, via del Fosso del Fiorano 65, 00143 Rome, Italy ABSTRACT 2-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptor. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammation. In this review, we describe the biosynthetic and metabolic pathways of 2-AG and how chemical and genetic perturbation of these pathways has led to insight in the biological role of this signaling lipid. Finally, we discuss the potential therapeutic benefits of modulating 2-AG levels in the brain. 1. Introduction [24–26], locomotor activity [27,28], learning and memory [29,30], epileptogenesis [31], neuroprotection [32], pain sensation [33], mood 2-Arachidonoylglycerol (2-AG) is one of the most extensively stu- [34,35], stress and anxiety [36], addiction [37], and reward [38]. CB1 died monoacylglycerols. It acts as an important signal and as an in- receptor signaling is tightly regulated by biosynthetic and catabolic termediate in lipid metabolism [1,2].
    [Show full text]
  • Introduction
    INTRODUCTION 1 1.1 Cannabis The hemp plant Cannabis sativa L., (Cannabaceae), native to Central Asia (probably north Afghanistan) has been used for medicinal purposes for millenia across many cultures. The first evidence of its therapeutic properties dates back to a description of the drug in a Chinese compendium of medicines at the time of the Chinese emperor Shen Nung dated 2737 B.C. In the 19th century the drugs were widely prescribed in the Western world for the treatment of cough, fatigue, rheumatism, asthma, delirium tremens, migraine headache, constipation and dysmenorrhea (Grinspoon, 1969). In addition to its great therapeutic potential, cannabis is known by numerous names such as marijuana, weed, blow, gear, grass and is the most commonly used illicit drugs among recreational substance abusers throughout the world. In many countries statistics quote that more than 50 % of young people have used it at least once (Iversen, 2005). The possession of cannabis was first banned in 1915, in California. Although cannabis became illegal in the USA, it was in the British pharmacopoeia and was occasionally used until 1971 when its use was outlawed in Misuse of Drugs Act (Baker et al., 2003). The most probable reason for the abuse is the action of the main psychoactive component of marijuana, (-)-∆9–tetrahydrocannabinol (∆9–THC), on the central nervous system (CNS), affecting cognition, memory and mood. After long-term cannabis use, mostly at high intake levels there is some evidence about it causing psychosocial harm to the user (lower educational achievement, 2 psychiatric illnesses- schizophrenia, depression, anxiety) but by comparison with other „recreational‟ drugs, cannabis is a relatively safe drug (Iversen, 2005).
    [Show full text]
  • Kannabinoidlerin Farmakolojisi
    KANNABİNOİDLERİN FARMAKOLOJİSİ Prof. Dr. Ahmet ULUGÖL Trakya Üniversitesi Tıp Fakültesi Tıbbi Farmakoloji Anabilim Dalı Kannabis (kenevir) esrar, marijuana, haşiş Kannabinoidler Fitokannabinoidler (doğal kannabinoidler) Sentetik kannabinoidler ve analogları Endokannabinoidler Araşidonil etanolamin (anandamid, AEA) 2-araşidonilgliserol (2-AG), vb. Fitokannabinoidler Δ9-tetrahidrokannabinol (THC) (psikoaktif) Kannabidiol (CB reseptörlere afinite, psikoaktif değil) Kannabinol Δ9-tetrahidrokannabivarin Δ9-tetrahidrokannabiorkol Kannabigerol Kannabikromen, vb. Sentetik kannabinoidler ve analogları Dronabinol (sentetik THC, Marinol) Nabilon (dronabinol analogu, Cesamet) THC + kannabidiol (Nabiximols, Sativex) Levonantradol, metanandamid WIN 55,212-2, HU-210, CP 55,940 CT-3 (ajulemik asit) rimonabant (SR141716A, Acomplia), vb. Endokannabinoidler Endokannabinoi CB1 CB2 TRPV1 d Anandamid +++ + + 2-AG +++ ++ 0 Virodhamin Agonist/parsiyel + 0 agonist N-araşidonil-dopamin +++ 0 +++ Noladin ether +++ + 0 CB1 & CB2 reseptörlerinin dağılımı CB1 CB2 immun sistem: dalak, tonsiller, timus - microglia, makrofaj, mast hücresi, vb. Kannabinoid reseptörlerinin sinyal ileti mekanizmaları Mekanizma Reseptör Gi/O protein aktivasyonu CB1/CB2 Adenilil siklaz inhibisyonu CB1/CB2 Kalsiyum kanallarının blokajı CB1 Potasyum kanallarının aktivasyonu CB1 MAPK aktivasyonu CB1/CB2 Kannabinoid tetradı Lokomotor aktivitede Hipotermi Katalepsi Analjezi Fizyolojik sistemlere etkiler Santral sinir sistemi Öfori-kannabinoid sarhoşluğu İntellektüel ve
    [Show full text]
  • SYNTHESIS of 3-HETEROCYCLE PHENYL N-ALKYL CARBAMATES and THEIR ACTIVITY AS FAAH INHIBITORS Doctoral Dissertation
    TKK Dissertations 203 Espoo 2009 SYNTHESIS OF 3-HETEROCYCLE PHENYL N-ALKYL CARBAMATES AND THEIR ACTIVITY AS FAAH INHIBITORS Doctoral Dissertation Mikko Myllymäki Helsinki University of Technology Faculty of Chemistry and Materials Sciences Department of Chemistry TKK Dissertations 203 Espoo 2009 SYNTHESIS OF 3-HETEROCYCLE PHENYL N-ALKYL CARBAMATES AND THEIR ACTIVITY AS FAAH INHIBITORS Doctoral Dissertation Mikko Myllymäki Dissertation for the degree of Doctor of Philosophy to be presented with due permission of the Faculty of Chemistry and Materials Sciences for public examination and debate in Auditorium KE2 (Komppa Auditorium) at Helsinki University of Technology (Espoo, Finland) on the 19th of December, 2009, at 12 noon. Helsinki University of Technology Faculty of Chemistry and Materials Sciences Department of Chemistry Teknillinen korkeakoulu Kemian ja materiaalitieteiden tiedekunta Kemian laitos Distribution: Helsinki University of Technology Faculty of Chemistry and Materials Sciences Department of Chemistry P.O. Box 6100 (Kemistintie 1) FI - 02015 TKK FINLAND URL: http://chemistry.tkk.fi/ Tel. +358-9-470 22527 Fax +358-9-470 22538 E-mail: [email protected] © 2009 Mikko Myllymäki ISBN 978-952-248-240-2 ISBN 978-952-248-241-9 (PDF) ISSN 1795-2239 ISSN 1795-4584 (PDF) URL: http://lib.tkk.fi/Diss/2009/isbn9789522482419/ TKK-DISS-2686 Multiprint Oy Espoo 2009 3 AB HELSINKI UNIVERSITY OF TECHNOLOGY ABSTRACT OF DOCTORAL DISSERTATION P.O. BOX 1000, FI-02015 TKK http://www.tkk.fi Author Mikko Juhani Myllymäki Name of the dissertation
    [Show full text]
  • Analysis of Natural Product Regulation of Cannabinoid Receptors in the Treatment of Human Disease☆
    Analysis of natural product regulation of cannabinoid receptors in the treatment of human disease☆ S. Badal a,⁎, K.N. Smith b, R. Rajnarayanan c a Department of Basic Medical Sciences, Faculty of Medical Sciences, University of the West Indies, Mona, Jamaica b Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA c Jacobs School of Medicine and Biomedical Sciences, Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY 14228, USA article info abstract Available online 3 June 2017 The organized, tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many Keywords: biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review Drug dependence/addiction will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling GTPases as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular Gproteins disease and cancer. While endogenous ligands are crucial for dispatching messages through the ECS, there are G protein-coupled receptor also commonalities in binding affinities with copious exogenous ligands, both natural and synthetic. Therefore, Natural products this review provides a comparative analysis of both types of exogenous ligands with emphasis on natural prod- Neurodegenerative disorders ucts given their putative safer efficacy and the role of Δ9-tetrahydrocannabinol (Δ9-THC) in uncovering the ECS. Efficacy is congruent to both types of compounds but noteworthy is the effect of a combination therapy to achieve efficacy without unideal side-effects.
    [Show full text]
  • Laws, Rules, and Regulations
    LAWS, RULES, AND REGULATIONS August 2020 Asa Hutchinson, Governor John Clay Kirtley, Pharm.D. Executive Director Arkansas Department of Health Arkansas State Board of Pharmacy 322 South Main Street, Suite 600 Little Rock, AR 72201 Phone: 501.682.0190 Fax: 501.682.0195 [email protected] www.pharmacyboard.arkansas.gov 10/8/2020 Arkansas State Board of Pharmacy Members Lenora Newsome, P.D. President, Smackover Rebecca Mitchell, Pharm.D. Vice President/Secretary, Greenbrier Deborah Mack, P.D. Member, Bentonville Lynn Crouse, Pharm.D. Member, Lake Village Brian Jolly, Pharm.D. Member, Beebe Carol Rader, RN Public Member, Fort Smith Amy Fore, MHSA, FACMPE, FACHE Public Member, Fort Smith 10/8/2020 Board of Pharmacy Law Book - Acts Table of Contents Pharmacy Practice Act A 17-92-101 Definitions……………………………………………………… 1-4 17-92-102 Exemptions…………………………………………………….. 4-5 17-92-103 Pharmacy laws unaffected……………………………………... 5 17-92-104 Privilege tax unaffected……………………………………….. 5 17-92-105 Prohibited acts – Penalties……………………………………... 6 17-92-106 Injunctions……………………………………………………… 6 17-92-107 Prosecutions – Disposition of fines……………………………. 6 17-92-108 Fees…………………………………………………………….. 6-10 17-92-109 Prescriptions for optometrists………………………………….. 10 17-92-110 Prescriptive authority of advance practice nurses……………… 10 17-92-111 Construction of Acts 1997, No. 1204………………………….. 10 17-92-112 Prescriptions for physician assistants…………………………. 10 17-92-201 Members – Qualifications……………………………………… 11 17-92-202 Members – Oath……………………………………………… 11 17-92-203 Members – Compensation…………………………………….. 11 17-92-204 Organization and proceedings…………………………………. 12 17-92-205 Rules and regulations – Enforcement………………………….. 12-13 17-92-206 Issuance of bulletins – Annual Reports………………………... 14 17-92-207 Maintenance of office………………………………………….
    [Show full text]
  • A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain
    Clinical and Translational Science Institute Centers 1-1-2018 The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain Giulia Donvito Virginia Commonwealth University Sara R. Nass West Virginia University Jenny L. Wilkerson Virginia Commonwealth University Zachary A. Curry Virginia Commonwealth University Lesley D. Schurman Virginia Commonwealth University See next page for additional authors Follow this and additional works at: https://researchrepository.wvu.edu/ctsi Part of the Medicine and Health Sciences Commons Digital Commons Citation Donvito, Giulia; Nass, Sara R.; Wilkerson, Jenny L.; Curry, Zachary A.; Schurman, Lesley D.; Kinsey, Steven G.; and Lichtman, Aron H., "The Endogenous Cannabinoid System: A Budding Source of Targets for Treating Inflammatory and Neuropathic Pain" (2018). Clinical and Translational Science Institute. 717. https://researchrepository.wvu.edu/ctsi/717 This Article is brought to you for free and open access by the Centers at The Research Repository @ WVU. It has been accepted for inclusion in Clinical and Translational Science Institute by an authorized administrator of The Research Repository @ WVU. For more information, please contact [email protected]. Authors Giulia Donvito, Sara R. Nass, Jenny L. Wilkerson, Zachary A. Curry, Lesley D. Schurman, Steven G. Kinsey, and Aron H. Lichtman This article is available at The Research Repository @ WVU: https://researchrepository.wvu.edu/ctsi/717 Neuropsychopharmacology REVIEWS (2018) 43, 52–79 © 2018 American
    [Show full text]
  • 2012 Meeting Program
    30th Annual Meeting of the South Central Chapter of the Society of Toxicology “Advancing Toxicology for 30 Years” November 1-2, 2012 Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 30th Annual Meeting of the South Central Chapter of the Society of Toxicology November 1-2, 2012 Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR “Advancing Toxicology for 30 Years” Thursday, November 1 Juanita’s, 614 President Clinton Ave., Little Rock, AR 6:30 – 9:00 PM Reception - Fajita Feast with cash bar Sponsored by Center for Toxicology & Environmental Health LLC Friday, November 2 Donald W. Reynolds Institute on Aging University of Arkansas for Medical Sciences Little Rock, AR 7:30 – 8:00 AM Continental Breakfast 8:00 – 8:15 AM Welcome & Opening Remarks Dr. Martin Ronis, Chair Local Organizing Committee Dr. Barbara Parsons, President SCC-SOT 8:15 – 9:15 AM Keynote Address – Dr. Russell S. Thomas Senior Investigator and Director of the Institute for Chemical Safety Sciences at The Hamner Institutes for Health Sciences, Research Triangle Park, NC. “Incorporating New Technologies into Toxicity Testing and Risk Assessment: Moving from 21st Century Vision to a Data- Driven Framework” 9:15 – 9:30 AM Jone Corrales, University of Mississippi, “Transcriptome analyses of benzo[a]pyrene exposure in zebrafish embryos and larvae” (Platform Presentation 1) 9:30 – 9:45 AM Syed Z. Imam, US FDA/National Center for Toxicological Research, “Hyperglycemia mitigates Parkinson’s disease: in vitro, animal model and clinical epidemiologic evidence” (Platform Presentation 2) 9:45 – 10:00 AM Sarah J.
    [Show full text]
  • Compartmentalization of Endocannabinoids Into Lipid Rafts In
    British Journal of DOI:10.1111/j.1476-5381.2011.01380.x www.brjpharmacol.org BJP Pharmacology Themed Section: Cannabinoids in Biology and Medicine, Part II Correspondence Neta Rimmerman, Arison Building 302, Department of RESEARCH PAPERbph_1380 2436..2449 Neurobiology, Weizmann Institute of Science, Rehovot, 76100, Israel. E-mail: [email protected] Compartmentalization of ---------------------------------------------------------------- Keywords cannabinoid; endocannabinoid; endocannabinoids into lipid lipid raft; membrane raft; microglia; Caveolin-1; flotillin-1; cannabidiol; CB1 receptor; mass rafts in a microglial cell line spectrometry ---------------------------------------------------------------- devoid of caveolin-1 Received 5 December 2010 Revised Neta Rimmerman1, Heather B Bradshaw2, Ewa Kozela3, Rivka Levy1, 3 March 2011 Ana Juknat3 and Zvi Vogel3 Accepted 10 March 2011 1Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel, 2Psychological and brain sciences, Indiana University, Bloomington, IN, USA, and 3Department of Physiology and Pharmacology, Sakler School of Medicine, the Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Tel Aviv University, Ramat Aviv, Israel BACKGROUND AND PURPOSE N-acyl ethanolamines (NAEs) and 2-arachidonoyl glycerol (2-AG) are endogenous cannabinoids and along with related lipids are synthesized on demand from membrane phospholipids. Here, we have studied the compartmentalization of NAEs and 2-AG into lipid raft fractions isolated from the caveolin-1-lacking microglial cell line BV-2, following vehicle or cannabidiol (CBD) treatment. Results were compared with those from the caveolin-1-positive F-11 cell line. EXPERIMENTAL APPROACH BV-2 cells were incubated with CBD or vehicle. Cells were fractionated using a detergent-free continuous OptiPrep density gradient. Lipids in fractions were quantified using HPLC/MS/MS.
    [Show full text]